1. CELL DIFFERENTIATION & EPIGENETICS

2. CELL DIFFERENTIATION Essential Question: How do complex organisms arise from a single cell?

3. Stem Cells and Differentiation All cells initially arose from the fertilized egg. Your body contains about 200 different types of cells that make up our tissues and organs. Questions to consider: What controls differentiation? How did each cell differentiate to make you the complex organism that you are? Stem Cells!

4. What controls differentiation? Controlled by genes Genes instruct each cell how and when to build the proteins that allow it to create the structures specific to the type of cell. Every nucleus of every cell contains the SAME DNA! Certain genes are activated while others remain inactive. Regulatory proteins turn genes on or off and account for the cell to “remember” what it should be doing long term.

5. Types of Stem Cells A stem cell is an undifferentiated cell that can develop and become specialized into different types of cells. Embryonic stem cells Obtained from embryos Adult stem cells Body cells that can differentiate into some other cell types Induced pluripotent stem cells Body cells that have been induced to return to a stem-cell-like state

6. Types of Stem Cells Totipotent – can form ANY type of cell Multipotent – can form many different types of cells Pluripotent – can form a few different types of cells

7. Embryonic Stem Cells & Differentiation Blastocyst has totipotent stem cells (5-7 days old) Blastulation occurs and the inner cell mass differentiates into three layers: These are multipotent stem cells (2-3 weeks old) Endoderm – D evelop into the gut tube: liver, GI tract, lungs, Mesoderm – Develop into heart, reproductive organs, blood, smooth muscle Ectoderm – Develop into brain, sensory organs, skin

8. Types of Cell Signaling Direct Contact – especially important in embryonic development Release factors to themselves or nearby cells; nervous system works this way Hormones – travel longer distances; travel through the blood stream Environmental Factors Direct - food we eat Indirect – stress which triggers hormones to be released

9. Determination of Stem Cell Fate When stem cells divide… One new cell will be differentiated One new cell will remain a stem cell With each division, the stem cell lineage is replenished so that the body continually has stem cells throughout life. This way any cell can be made throughout life.

11. Stem Cells as a Medical Treatment Testing new drugs – Scientists are able to mimic differentiation allowing them to test drugs on the specific type of cells the drug is designed for. Scientists are still unable to reproduce all the tissues as in nature due to the environment and exact signaling that occurs. Cell-based therapies – Treatment in which stem cells are induced to differentiate into the specific cell type required to repair damaged or destroyed cells or tissues. Used to treat diseases such as: macular degeneration, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis. To summarize, stem cells offer exciting promise for future therapies, but significant technical hurdles remain that will only be overcome through years of intensive research.

12. EPIGENETICS Essential Question: Is DNA really your destiny?

13. Video – Epigenome, the symphony in your cells. (stop at 1:50) http://www.nature.com/news/epigenome-the-symphony- in-your-cells-1.16955 http://www.nature.com/news/epigenome-the-symphony- in-your-cells-1.16955

14. What is epigenetics? Epigenome literally means above the gene. Epi – above Genome - the complete set of genes in a cell or organism. Structure of DNA The double helix of DNA is wrapped around special proteins called histones.

15. Does your DNA change throughout your life? Yes and No The DNA code you were born with remains the same (the sequence of nucleotides), the expression of those genes can change – that is your epigenome. Epigenetic change is a regular and natural occurrence. The epigenome you were born with is not the same as your current epigenome.

16. What factors influence our epigenome? Epigenome is influenced by factors such as Age Environment Famine vs. plentiful food supply Pollutants in the environment – heavy metals, pesticides, diesel exhaust, tobacco smoke (2 nd hand smoke), radioactivity Lifestyle Basic nutrient levels – fast food diet vs. organic whole foods diet Stress levels Smoking, drinking, drug usage Disease state Viruses bacteria

18. Effects of epigenetic change Epigenetic changes can cause: Disease – Alzheimer's, cancer, autism Genes to be amplified – proteins are produced more often Genes to be slowed down – proteins are produced less often

19. Video – Epigenome, the symphony in your cells. (start at 1:50) http://www.nature.com/news/epigenome-the-symphony- in-your-cells-1.16955 http://www.nature.com/news/epigenome-the-symphony- in-your-cells-1.16955

20. Mechanisms of epigenome change DNA Methylation – addition or removal of a methyl group (CH 3 ) Acetylation – modifies the chromatin around the histones. Tightly folded chromatin tends to be shut down, or not expressed, while more open chromatin is functional, or expressed. HONORS

21. Changes can effect offspring Imprinting – Certain genes are expressed in a parent-of-origin- specific manner. If the allele (variety of gene; ie. hairy vs. not hairy) inherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed. Occurs by either methylation or acetylation. Could be problematic if the expressed allele is damaged or increases vulnerability to diseases. Due to imprinting, changes can even be passed on to your offspring - up to four generations. The offspring may however change its own epigenome based on the already discussed factors. HONORS

22. Example #1 of Epigenetic Changes Rats - In rats, licking, grooming, and nursing methods that mother rats use with their pups can affect the long-term behavior of their offspring. The pups that were nurtured more better respond to stress levels in the future. The licking and grooming caused the glucocorticoid receptor gene to make more receptors to bind to stress hormones in times of high stress, causing the rat pup to be more resilient to stress. In contrast, the pups that were ignored when young do not produce many receptors to bind to the stress hormones resulting in low resilience to stress.

23. Example #2 of Epigenetic Changes Dutch Famine – Mothers that experienced famine during the first few month of pregnancy, then were provided with adequate food the remaining gestation had babies normal birth weight. When the babies were revisited later in life, they had a high obesity rates, greater incidence of health problems, and mental illnesses. Mothers that experienced malnutrition during conception and the last few months of pregnancy, the baby had low birth weight. When the babies were revisited later in life, no matter how much food was available to them their bodies never got over the period of malnutrition.

24. Video about Epigenetics (5 min) http://vegas.pbslearningmedia.org/resource/biot09.sci.life.gen.epigenetics/epi genetics / http://vegas.pbslearningmedia.org/resource/biot09.sci.life.gen.epigenetics/epi genetics / Discussion Questions: 1. In what way do the brown and yellow mice shown in the video differ? Why is this so? 2. Explain how two genetically identical twins are not really identical. 3. Explain why DNA from an older twin set differs more significantly than the DNA of a younger twin set. What factors could account for this?

25. Crash Course – Epigenetics (9 min) https://www.youtube.com/watch?v=kp1bZEUgqVI